Lecture 12 - Renal Regulation of Acid-Base Balance Flashcards
In what 2 forms do the kidneys excrete H+ from the ECF? Which one predominates? Provide daily amounts.
- Titratable acid: 10 to 30 mEq/day
2. ***Ammonium (NH4+): 30 to 50 mEq/day
Equation for net acid excretion? Unit?
NAE (mEq/day) = (UTA.V + UNH4+.V) - UHCO3-.V
Normal net acid excretion?
40-80 mmol/day
Describe the pH of tubular fluid.
Tubular fluid at bowman’s space has the same pH as plasma (7.4) and will be acidified to be excreted as acid
What is titratable acid?
To determine that amount in urine we just add base until the pH has reached 7.4 (titration), which is why we called it that = urinary buffers that can accept H+
Why doesn’t urine titration capture urine NH4+?
Because the pKa of NH4+ is >9
9 factors regulating renal acid excretion?
- GFR
- Tubular HCO3- reabsorption
- H+ secretion
- Ammoniagenesis
- PCO2
- ECF volume
- K+ balance
- Aldosterone
- Ang II
How does GFR regulate renal acid excretion?
As GFR falls, the kidney’s ability to excrete an acid load will decrease
Describe tubular HCO3- reabsorption/secretion to regulate renal acid excretion.
- PCT and THICK ASCENDING LIMB: Na+/H+ exchanger: H+ is secreted and reacts with HCO3- to form H2O and CO2 by lumenal carbonic anhydrase, which diffuse into the proximal tubule cells. HCO3- in then reformed by carbonic anhydrase inside the cell and exits via the basolateral membrane via facilitated diffusion => NET EFFECT: 1 Na+ reabsorbed = 1 H+ pumped out = 1 HCO3- reabsorbed
- Collecting duct:
2a. ALPHA-intercalated cell:
- H+-ATPase: H+ is secreted and reacts with HCO3- to form H2O and CO2 by lumenal carbonic anhydrase, which diffuse into the proximal tubule cells. HCO3- in then reformed by carbonic anhydrase inside the cell and exits via the basolateral membrane via Cl-/HCO3- exchanger => NET EFFECT: H+ pumped out = 1 HCO3- reabsorbed
2b. BETA-intercalated cell:
- HCO3-/Cl- lumenal exchanger with H+-ATPase on the basolateral side: H2O and CO2 converted to HCO3- and H+ by carbonic anhydrase inside the cell and then HCO3- is secreted into lumen and H+ is reabsorbed by the blood
Where is HCO3- reabsorbed in the nephron? Provide %.
- Proximal tubule: 85%
- Thick ascending limb of loop of Henle: 10%
- Collecting duct: 5%
Excretion fraction of HCO3-?
0% (unless we are on a vegan diet or ingest excess base)
Permeability of HCO3- in proximal tubule and thick ascending limb of the loop of Henle?
HCO3- is impermeable intra and paracellularly
What hormone stimulates the reabsorption of HCO3-? Explain how.
Angiotensin II:
- Stimulates Na+/H+ exchanger in the proximal tubule and thick ascending limb of the loop of Henle
- Stimulate H+ secretion via H+ ATP-ase pump insertion on lumenal membrane of intercalated cells of collected duct causing more Na+ reabsorption on the lumenal surface => causing the Na+/K+-ATPase to pump more Na+ out on basolateral suface => further Na+ reabsorption
pH of tubular fluid in early distal tubule? Implication
6.8
Ideal buffer at this point is HPO42-/H2PO4- because its pKa = 6.8
Concentration of FREE H+ in maximally acidified urine? What does this mean for urine acid?
[H+] = 10^(-4.4) = 0.04 mmol/L
Means that only 0.06 mmol of free H+ excreted in a day => most acid in the urine is NOT free but bound to urinary buffers
What are urinary buffers? What is this referred to in urine?
- HPO42-
- SO42-
=> titratable acids
Are the set amounts of alpha and beta intercalated cells in the collecting duct?
NOPE - ability of intercalated cells to adjust:
Acidosis => H+-ATPase vesicles migrate to lumenal membrane and HCO3-/Cl vesicles migrate to the basolateral membrane => alpha-intercalated cell
Alkalosis => H+-ATPase vesicles migrate to basolateral membrane and HCO3-/Cl vesicles migrate to the lumenal membrane => beta-intercalated cell
Where does H+ being secreted by the proximal tubule/TAL/CD to create TAs come from? Purpose?
Comes from CO2 + H2O reacting to form H+ + HCO3- => NEW HCO3- reabsorbed by the peritubular plasma to restore the lost plasma base used to buffer the acid load
Purpose of ammoniagenesis?
Amount of urinary buffers in tubular fluid is limited (Pi excretion is regulated based on Pi needs, not AB status), so we need another way to accept H+ and excrete it
Describe renal ammoniagenesis. Result?
- Glutaminase: glutamine => glutamate + NH4+
- Glutamate dehydrogenase: glutamate => alpha-ketoglutarate + NH4+
RESULT: NH4+ excreted and HCO3- generated
How does excreting NH4+ spare HCO3-? Which reason do we use to account for it?
TWO REASONS
REASON 1:
Production of urea in the liver: NH4+ + CO2 => urea + 2 H+ => 2H+ need to be buffered by 2 HCO3-
BUT, if you excrete NH4+ directly, without converting it to urea, then you spare those 2 HCO3- => aka you kinda generate them
REASON 2:****
As NH4+ goes through the nephron, in the thick ascending limb, NH4+ takes the place of K+ in the Na+/K+/2Cl- carrier => in the cell it splits into ammonia (NH3) and H+ => H+ used to reabsorb HCO3- through the H+/Na+ exchanger and NH3+ diffuses in outer medulla and into the collecting duct => H+ secreted by intercalated cells reacts with NH3 to produce NH4+ and a NEW HCO3- which is reabsorbed
Purpose of urea?
Protein excretion
What segment of nephron performs ammoniagenesis? How is it secreted into the lumen?
Proximal tubule
NH4+ takes the place of H+ in the Na+/H+ lumenal exchanger
Ammonia?
NH3
